Non-Proteolytic Aeroallergens from Mites, Cat and Dog Exert Adjuvant-Like Activation of Bronchial Epithelial Cells

Österlund, Camilla; Grönlund, Hans; Gafvelin, Guro; Bucht, Anders

doi:10.1159/000318743

Cited by 25 publications

(22 citation statements)

References 72 publications

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“…The most likely lung cells regulated by GSTM1 are bronchial epithelial and smooth muscle cells that express GSTM1 (7) and are capable of generating proneutrophilic cytokines after exposure to allergens (35). We did not find regulation by allergens of other proneutrophilic cytokines previously associated with asthma, including IL-17, a T cell-dependent cytokine (26); IL-33, a chromatin-associated nuclear cytokine from the IL-1 family of cytokines (27); and CXCL1 (36).…”

Section: Discussionmentioning

confidence: 64%

“…However, the GSTM1-dependent restraining mechanism could be disrupted in the atopic asthmatic airways as a result of down-regulation of the transcription factor nuclear factor (erythroid-derived 2)-like 2 (38, 39) controlling expression of GSTM1 (40). Airway epithelial cells could be particularly affected as they express GSTM1 (7) and are capable of generating robust proneutrophilic signals after allergen stimulation (35). A tight regulation of stress-signaling pathways would suggest the presence of an alternative inhibitory mechanism in GSTM1 2 individuals.…”

Section: Discussionmentioning

confidence: 99%

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Asthmatic Airway Neutrophilia after Allergen Challenge Is Associated with the Glutathione S-Transferase M1 Genotype

Hoskins

Reiss

et al. 2013

Am J Respir Crit Care Med

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Rationale: Asthma is a heterogeneous lung disorder characterized by airway inflammation and airway dysfunction, manifesting as hyperresponsiveness and obstruction. Glutathione S-transferase M1 (GSTM1) is a multifunctional phase II enzyme and regulator of stress-activated cellular signaling relevant to asthma pathobiology. A common homozygous deletion polymorphism of the GSTM1 gene eliminates enzyme activity. Objectives: To determine the effect of GSTM1 on airway inflammation and reactivity in adults with established atopic asthma in vivo. Methods: Nineteen GSTM1 wild-type and eighteen GSTM1-null individuals with mild atopic asthma underwent methacholine and inhaled allergen challenges, and endobronchial allergen provocations through a bronchoscope. Measurements and Main Results: The influx of inflammatory cells, panels of cytokines and chemokines linked to asthmatic inflammation, F 2 -isoprostanes (markers of oxidative stress), and IgE were measured in bronchoalveolar lavage fluid at baseline and 24 hours after allergen instillation. Individuals with asthma with the GSTM1 wild-type genotype had greater baseline and allergen-provoked airway neutrophilia and concentrations of myeloperoxidase than GSTM1-null patients. In contrast, the eosinophilic inflammation was unaffected by GSTM1. The allergen-stimulated generation of acute-stress and proneutrophilic mediators, tumor necrosis factor-a, CXCL-8, IL-1b, and IL-6, was also greater in the GSTM1 wild-type patients. Moreover, post-allergen airway concentrations of IgE and neutrophilgenerated mediators, matrix metalloproteinase-9, B-cell activating factor, transforming growth factor-b1, and elastase were higher in GSTM1 wild-type individuals with asthma. Total airway IgE correlated with B-cell activating factor concentrations. In contrast, levels of F 2 -isoprostane were comparable in both groups. Finally, GSTM1 wild-type individuals with asthma required lower threshold concentrations of allergen to produce bronchoconstriction. Conclusions: The functional GSTM1 genotype promotes neutrophilic airway inflammation in humans with atopic asthma in vivo.Keywords: atopic asthma; GSTM1 polymorphism; inflammatory asthma phenotypes; neutrophilic airway inflammation Asthma is a heterogeneous airway disorder characterized by inflammation, hyperresponsiveness, and obstruction. There is considerable interest in classifying asthma phenotypes. It has been suggested that the type of airway inflammation might define asthma phenotypes. One proposed classification uses eosinophilic, neutrophilic, and paucigranulocytic cellular inflammation to define three subtypes of asthma (1). The neutrophilic inflammation has recently drawn more attention because of its association with severe asthma and poor response to corticosteroids (2). The relationship between various asthmatic phenotypes and genotypes in humans is poorly understood.Glutathione S-transferase M1 (GSTM1) is a phase II cytoprotective protein from the family of cytosolic GSTs (3). The GSTM1 gene is located on chromosome 1p13.3 and ha...

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Asthmatic Airway Neutrophilia after Allergen Challenge Is Associated with the Glutathione S-Transferase M1 Genotype

Hoskins

Reiss

et al. 2013

Am J Respir Crit Care Med

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“…In addition, OGG-1 siRNA significantly inhibited IL-2, IL-4, and IL-17, while enhancing IFN-γ. It is worth noting that there are differences in cytokine expression between the OVA and HDM models as HDM extracts induce inflammation, largely as a result of their protease activities (65). Nevertheless, our HDM in vitro model identified a potential regulatory role for OGG-1 in ROS levels because anti-oxidants prevented the increase in ROS and OGG-1 levels following HDM challenge.…”

Section: Discussionmentioning

confidence: 99%

8-Oxoguanine-DNA glycosylase 1 deficiency modifies allergic airway inflammation by regulating STAT6 and IL-4 in cells and in mice

Yuan

Yan

et al. 2012

Free Radical Biology and Medicine

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8-oxoguanine-DNA glycosylase (OGG-1) is a base excision DNA repair enzyme; however, its function in modulating allergic diseases remains undefined. Using OGG-1 knockout (KO) mice, we show that this protein impacts allergic airway inflammation following sensitization and challenge by ovalbumin (OVA). OGG-1 KO mice exhibited less inflammatory cell infiltration and reduced oxidative stress in the lungs after OVA challenge compared to WT mice. The KO phenotype included decreased IL-4, IL-6, IL-10, and IL-17 in lung tissues. In addition, OGG-1 KO mice showed decreased expression and phosphorylation of STAT6 as well as NF-κB. Down-regulation of OGG-1 by siRNA lowered ROS and IL-4 levels but increased INF-γ production in cultured epithelial cells following exposure to house dust mite (HDM) extracts. OGG-1 may affect the levels of oxidative stress and proinflammatory cytokines during asthmatic conditions. OGG-1-deficiency negatively regulates allergen-induced airway inflammatory response.

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“…One such mechanism is the bronchial epithelium's hyporesponsiveness towards Gram-positive bacteria, due to low expression of TLR2 and a lack of expression of CD36, which mediates the phagocytosis of Gram-positive bacteria [35,36]. Others have shown that certain microorganisms or aeroallergens may function as adjuvants for epithelial activation in both protease-dependent and independent manners [37,38]. The airway epithelium also maintains a steady-state condition by producing anti-inflammatory cytokines, such as TGF-β and indoleamine 2,3-dioxygenase, which suppress T cell-mediated immunity, as well as the activation of antigen-presenting cells [34,39].…”

Section: The Airway Epitheliummentioning

confidence: 99%

Polarized Airway Epithelial Models for Immunological Co-Culture Studies

Papazian

Würtzen

Hansen

2016

Int Arch Allergy Immunol

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Epithelial cells line all cavities and surfaces throughout the body and play a substantial role in maintaining tissue homeostasis. Asthma and other atopic diseases are increasing worldwide and allergic disorders are hypothesized to be a consequence of a combination of dysregulation of the epithelial response towards environmental antigens and genetic susceptibility, resulting in inflammation and T cell-derived immune responses. In vivo animal models have long been used to study immune homeostasis of the airways but are limited by species restriction and lack of exposure to a natural environment of both potential allergens and microflora. Limitations of these models prompt a need to develop new human cell-based in vitro models. A variety of co-culture systems for modelling the respiratory epithelium exist and are available to the scientific community. The models have become increasingly sophisticated and specific care needs to be taken with regard to cell types, culture medium and culture models, depending on the aim of the study. Although great strides have been made, there is still a need for further optimization, and optimally also for standardization, in order for in vitro co-culture models to become powerful tools in the discovery of key molecules dictating immunity and/or tolerance, and for understanding the complex interplay that takes place between mucosa, airway epithelium and resident or infiltrating immune cells. This review focuses on current knowledge and the advantages and limitations of the different cell types and culture methods used in co-culture models of the human airways.

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Non-Proteolytic Aeroallergens from Mites, Cat and Dog Exert Adjuvant-Like Activation of Bronchial Epithelial Cells

Cited by 25 publications

References 72 publications

Asthmatic Airway Neutrophilia after Allergen Challenge Is Associated with the Glutathione S-Transferase M1 Genotype

Asthmatic Airway Neutrophilia after Allergen Challenge Is Associated with the Glutathione S-Transferase M1 Genotype

8-Oxoguanine-DNA glycosylase 1 deficiency modifies allergic airway inflammation by regulating STAT6 and IL-4 in cells and in mice

Polarized Airway Epithelial Models for Immunological Co-Culture Studies

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